The osteoclast cytoskeleton is a unique structure that polarizes the cell's resorptive machinery to the bone–cell interface where it creates an isolated resorptive microenvironment consisting of an actin ring surrounding a ruffled border. This polarization process occurs under the aegis of the αvβ3 integrin in collaboration with the M-CSF receptor, c-Fms. When occupied, αvβ3 activates a canonical signaling complex consisting of c-Src, Syk, Dap12, Slp76, Vav 3, and Rac that permits the cell to spread and form actin rings. Generation of the ruffled border, the cell's resorptive organelle, is an exocytic process wherein synaptotagmin VII mediates fusion of secretory lysosomes to the bone-apposed plasma membrane. Absence of any component of this signaling pathway compromises osteoclast cytoskeletal organization and abridges bone resorption.